Indoles are industrially useful substances as starting material for the preparation of perfumes, amino acids such as tryptophane, and stabilizers for high polymers. They are also important intermediates in the dyestuffs industry. Indoles are also contained in numerous drugs that are already on the market in the pharmaceutical agent or as an intermediate compound en route to the final target compound.
Substituted indoles have frequently been referred to as privileged structures since they are capable of binding to multiple receptors with high affinity, and thus have applications across a wide range of therapeutic areas. As a result, indole ring system is an important building block or intermediate in the synthesis of many pharmaceutical agents. Notably, indole-3-carbinol, found in cruciferous vegetables, inhibits carcinogenesis at the initiation stage and has been shown to inhibit carcinogenesis in several animal species.
Various attempts have been carried out for the synthesis of indoles. For example, one of the most prevalent processes to prepare indoles is the Fischer indole synthesis, which involves producing indoles from a phenylhydrazine and an aldehyde or ketone. However, the process suffers from drawbacks such as the need for acidic and harsh conditions, as well as limited commercial availability of hydrazines. Other known processes include the Bischler indole synthesis and the Larock indole synthesis. However, these known processes are accompanied by one or more problems in that the indole product yield is not high due to formation of by-products, expensive raw materials, and/or need for complex preparation steps.
In view of the above, there remains a need for improved methods to synthesize indoles that address at least one of the above-mentioned problems.